Mesenchymal stem cells induce endothelial activation via paracine mechanisms

Mesenchymal stem cells (MSCs) are bone marrow-derived, pluripotent cells that possess the ability to transdifferentiate into various mesenchymal tissues such as bone, endothelium, and (heart) muscle. Therefore, these cells may provide a therapeutic tool, especially for the treatment of myocardial infarction. The interaction of the MSCs with the endothelial barrier and their ability to ultimately leave blood vessels after application are crucial in this context. In this study, the authors focused on the soluble factors produced by MSCs and their effect on the intracellular signal transduction of endothelial cells. The authors performed immunohistochemical measurements on human umbilical vein endothelial cells (HUVECs) treated with conditioned stem cell medium and took measurements of the intracellular nitric oxide (NO) levels and calcium changes. After application of conditioned stem cell medium, the authors detected an increase in endothelial NO synthase (eNOS) activity by translocation (Ca(2+)) and by phosphorylation (increase of pAKT and peNOS1177). Additionally, the authors observed an upregulation of pERK within the same time. The phosphorylated eNOS forms are linked to these findings and the increase of intracellular NO in the DAF measurements. Moreover, conditioned medium also increased intracellular calcium levels in endothelial cells. Concluding, the authors postulate that MSCs emit soluble factors that alter the NO and calcium levels of endothelial cells and may be important for facilitate crossing the endothelial barrier.